Optional AOM therapy: novel strategy

April 2002

Evidence from clinical trials which evaluated the need for antibiotic treatment of children with acute otitis media (AOM) have been subjected to careful meta-analysis. The results support the option of withholding antibiotics for uncomplicated AOM in children older than 2 years.

Definition of disease

I define AOM as an opacified, bulging, tympanic membrane with poor mobility. Often, the child will be fretful or complain of a painful ear. This definition excludes non-bulging tympanic membranes, regardless of degree of redness or degree of impaired mobility by pneumatic otoscopy. The definition of AOM in almost all the referenced studies varied from redness of the eardrum to bulging of an opacified, poorly mobile eardrum.

Obviously, any antibiotic or no antibiotic will seem effective when there is only OM with effusion or transient redness of the tympanic membrane. Moreover, several prerequisites for excellent otoscopy must be mandated in the study design, ie, use of well-designed aural specula, careful cleaning of wax and squamous debris from the ear canal, proper restraint of struggling children, and application of negative and positive pressure through the pneumatic otoscope.

Without these critical prerequisites, conclusions from any AOM study must be viewed with a jaundiced eye. Other important variables, which can impair a study’s validity, include reasons for exclusion from the study, the drop-out rate, the number of examiners of the children with different criteria for the diagnosis of AOM, and the complication rate for serious adverse events.

S. Michael Marcy, MD, a member of the AAP Subcommittee on Quality Improvement, has said that initial watchful waiting with analgesic treatment is one of the evolving principles being discussed by the committee. According to Marcy, there are nine studies that evaluated early outcomes of antibiotic treatment vs. placebo for children with AOM. Antibiotics did seem to reduce the duration of fever in two studies. Antibiotics did not seem to reduce the perception of pain at 24 hours but reduced pain perception by only one-third in the next few days.

The Netherlands is still the only country where only a minority of the episodes of AOM is treated with antibiotics. In a study of 5,000 Dutch children with AOM, only 3% of those older than 2 required antibiotics or myringotomy for management of severe disease. Guidelines for Dutch general practitioners also permit judicious withholding of antibiotics for children aged 6 months to 2 years. It should be underscored that the Netherlands reports that penicillin-resistant Streptococcus pneumoniae are infrequently isolated in that country (<5% of S. pneumoniae cultures).

Medical litigation does not produce the same degree of worry in the Netherlands as it does in the U.S. The seminal 1985 study by van Buchem excluded children younger than 2. Study participants who failed on watchful waiting or symptomatic treatment only were promptly reexamined by an otolaryngologist who was prepared to perform a myringotomy if required. The Cochrane Review of Antibiotics for AOM in children concluded, “Antibiotics provide a small benefit for AOM in children, particularly those populations living in areas where acute mastoiditis is uncommon.”

During the past six months, when I diagnosed uncomplicated AOM in a child who was not showing signs of severe pain or high fever, I encouraged many parents to accept a prescription for amoxicillin, 50 mg/kg/day, in two divided doses, but to withhold filling it unless their child experienced severe or protracted pain, high fever or other symptoms. My goal was to reduce antibiotics for AOM by at least 35%. Of course, recommendations were made to the parents to treat symptoms of fever and/or persistent pain.

There are important exclusions to this plan. Infants and children younger than 2 years (my cut-off point was a 6-month-old) should probably be excluded, although these comprise most children with AOM. Children who appear toxic at the time of diagnosis of AOM, those with high fever or intense and persistent otalgia should also be excluded, at least until well-designed clinical trials show that it is safe to withhold treatment from these subgroups. Should I also exclude children who had multiple previous episodes of AOM? What about those in a child-care setting?

Empowering parents

Giving parents the option to treat is certainly not a new idea, and perhaps, many readers have used it for some of their own patients. The inclusion of the parent in the decision to treat with an antibiotic for what is to most children a benign self-limited disease represents a compromise between the Dutch approach, which requires reconnect with medical providers before an antibiotic could be prescribed, and the U.S. approach, which is to prescribe antibiotics for almost all children with AOM.

The approach is a cooperative effort between parent and physician to reduce unnecessary antibiotic prescriptions. It is a third venue in between a “treat all” recommendation and treat only those who fail to improve after 48 to 72 hours of watchful waiting. It empowers the parent to treat, should clinical signs worsen or persist, yet it offers a safety net to reduce parental anxiety or anger and financial cost if the child were forced to return to the medical office after 48 hours to receive a prescription for an antibiotic.

In addition, I believe that there are other important safeguards to this third venue. Most children should have received three doses of conjugate pneumococcal vaccine (PVC7, Prevnar, Wyeth) by the 6-month routine check-up. In the latter half of their first year, they should have developed protective antibodies to the most common virulent serotypes of S. pneumoniae.

Group A streptococcal AOM is a potential problem with the watchful waiting approach. Although it is not possible to accurately predict the middle ear pathogen from the appearance of the eardrum or the intensity of pain, streptococcal AOM usually causes intense and persistent pain and tends to produce a very intensely inflamed tympanic membrane. Non-typeable strains of Haemophilus influenzae and all strains of Moraxella catarrhalis are not associated with serious complications of AOM such as acute mastoiditis, dural vein thrombophlebitis or brain abscess.

I don’t know if I convinced you that the middle approach is worth your consideration. I do know that two Institutional Review Boards (IRBs) did not approve my proposal for a self-funded study of 150 young children with AOM (Parental Optional Treatment with Amoxicillin for AOM). Their rejection, and reasons for it, cost me $750 and seriously dampened my enthusiasm for conducting a clinical trial in my practice. The IRBs felt the protocol was too dangerous for their approval.

Have any of you selectively withheld antibiotics from children with AOM? Was this approach acceptable to the parents? Do you know what percentage of parents filled the prescription within the next 24 hours? What are your thoughts on this middle-ground approach?

For more information:

• Appelman CLM, Bossen PC, Dunk JHM, et al. NHG standard otitis media acute. (Guideline on acute otitis media of the Dutch College of General Practitioners.) Huisarts Wet 1990;33:242-5.
• Burke P, Bain J, Robinson D, et al. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. BMJ 1991;303:558-62.
• Damoiseaux RAMJ, van Balen FAM, Hoes AW, et al. Primary care based randomized, double-blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ 2000;320:350-54.
• Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. BMJ 1997;314:1526-29.
• Glasziou PP, Del Mar CB, Hayem M, et al. Antibiotics for acute otitis media in children [Review]. Cochrane Database Syst Rev 2000;4:CD00219.
• Little P, Gould C, Williamson I, et al. Pragmatic randomized controlled trial of two prescribing strategies for childhood acute otitis media. BMJ 2001;322:336-42.
• Paradise JL. Treatment guidelines for otitis media: the need for breath and flexibility. Pediatr Infect Dis J 1995;14:429-35.
• Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial drugs for acute otitis media: meta analysis of 5400 children from thirty-three randomized trials. J Pediatr 1994;124:355-67.